National Cell Repository for Alzheimer Disease (NCRAD)

Transcription

1 National Cell Repository for Alzheimer Disease (NCRAD) Tatiana Foroud, Ph.D. Principal Investigator Indiana University School of Medicine U24AG21886

2 History of NCRAD 1990 Began to recruit families; bank DNA, LCLs 2002 Expanded to bank samples from other studies 2005 Expand efforts to bank additional sample types; serve as a repository for other studies 2015 Bank samples for 20+ studies

3 NCRAD and NACC goal For EVERYONE seen at an ADC, store uniform phenotypic data and a DNA sample Samples from 22,226 ADC subjects at NCRAD ADCs NCRAD NACC

4 ADC Blood Samples Major effort to encourage ADCs to send a blood sample for each subject seen at their ADC who has a UDS Received blood samples for 4,375 subjects 3,675 new individuals Some overlap with other samples that have been previously sent (DNA or buffy coat) and therefore aren t counted as a new unique sample on Phase 2 list

5 ADC Blood Samples Number of ADC Subjects

6 Samples Received at NCRAD from ADCs Phase 1 Phase 2 Total Brain Tissue 3, ,519 DNA ,772 12,042 Buffy Coat 0 1,519 1,519 Blood 0 3,675 3,675 Internal Transfer 3 1,468 1,471 Total 3,792 18,434 22,226 ~4,000 new unique samples since last year (> 20% increase)

7 ADC Sample Status at NCRAD Subjects with a UDS (n=31,105) Sample Not Received 4,159 8,512 Samples Received 8,436 9, ,000 4,000 6,000 8,000 10,000 12,000 Dead/Discontinued Active

8 NCRAD Sample Distribution Since Inception # of researchers 128 # of samples-dna 176,841 # of samples-blood 811 # of samples-cell lines 1,917 # of samples-plasma 3,600 # of samples-serum 100 # of samples-pbmc 7 There have been 394 publications citing the use of NCRAD samples. 95 publications in the past year, alone.

9 NCRAD Calls with the ADCs Completed the annual calls with all ADCs Reviewed sample contributions Reviewed available data and how to obtain in APOE, GWAS, WES Reviewed GDS policy Reviewed sample requests and grant numbers

10 ADSP Discovery Sample Timeline February February April November August Sequencing Initiative Announced ADSP Discovery Design Finalized Discovery Samples Selected All Discovery Samples at LSSC All Discovery Samples Sequenced

11 Alzheimer Disease Sequencing Project (ADSP) Discovery Phase Replication Phase Whole Genome Sequencing (WGS) 578 individuals from 111 families Follow-up Sequencing Whole Exome Sequencing (WES) 10,939 individuals 5,963 cases; 4,976 controls

12 ADSP Replication/Follow-up Designs Type Rationale Advantage Disadvantage 1 Custom Targeted Sequencing 2 Whole exome sequencing 3 Hybrid - Target sequence & WES Strong findings from WGS in nonexonic regions Promising regions poorly covered in WGS/WES Implemented if WGS and WES does not identify regions/variants to follow-up Promising findings from both WES and WGS Follow-up nonexonic signals Deeper sequence coverage Combine with Discovery WES to increase power New WES replicate Discovery WES Provide follow-up for WGS Only small region studied Challenging to design Assumes strong prior hypothesis Does not cover nonexonic regions May not provide followup for WGS findings Reduced sample size for both studies Lower power to replicate/follow-up findings

13 ADSP Replication/Follow-up Designs Targeted Sequencing WES 1 Yes No Targeted Sequencing (N) 35,000 (17,500 cases; 17,500 controls) 2 No Yes No 3 Yes Yes 5,750 (2,875 cases; 2,875 controls) WES (N) No 14,000 (7,000 cases; 7,000 controls) 11,500 (5,750 cases; 5,750 controls)

14 Replication/Follow-up Timeline January 2015 December 2015 April 2016 Analysis of ADSP Discovery Sample Replication RFAs written, reviewed & funded Replication Sample Genotyping & Analysis Potential studies obtain IRB certification& Institutional Signature Gather & centralize minimal phenotypic dataset for potential cases/controls Selection & Shipment of Replication Samples

15 What is Needed NOW? All studies/centers that may participate in the Replication/Follow-Up must obtain approvals New Genomics Data Sharing (GDS) Policy is in place GDS Requirements IRB approval Genomics language Consent group assignment Institutional Certificate Copy of Informed Consent Document

16 NCRAD/Indiana University Expansion Over the past few years. Expanded the scope of samples collected Expanded our role in many studies to provide more study coordination and training Expanded to other disorders

17 Sample Types at NCRAD DNA (genomic, brain, LCL) RNA (PAXgene blood tubes Plasma Serum CSF Brain Tissue Lymphoblastoid Cell Lines (LCLs) Peripheral Blood Mononuclear Cells (PBMCs)

18 NCRAD Role in Other Studies Previously, simply received samples for ongoing studies LOAD, ADNI, ADGC, DIAN, GIFT Now, providing study sample coordination Generate specimen processing manuals and videos Provide training to site coordinators for sample collection and processing Provide on demand kits through website portal Regular site and study specific reports

19 Study Sample Types Received # Sampled Subjects Genetic Epidemiology of Alzheimer s Disease in African Americans (AA Genetics Cell lines and DNA 1688 Study) (R01AG028786) African American GWAS Initiative Transferred DNA 2,444 Alzheimer s Disease Genetics Consortium (ADGC) (U01AG032984) Dominantly Inherited Alzheimer Network (DIAN Study) (U01AG032438) Genetic Consortium for Late Onset Alzheimer s Disease (LOAD Family Study) (U24AG and R01AG041797) NCRAD Family Study University of Kentucky ADC (UK-ADC) (P30AG028383) Washington University ADRC (WU-ADRC) (P50AG005681) AD Focused Studies DNA (Brain tissue, buffy coat, blood) PBMCs Transferred DNA aliquots and saliva 21,824 Cell lines and DNA 387 Cell lines and DNA DNA (Brain tissue and blood) Cell lines and DNA DNA (Brain tissue and blood) PBMCs Cell lines and DNA DNA (blood) Cell lines and DNA DNA (blood) 6,761 3,

20 More AD Focused Studies Study Alzheimer s Disease Patient Registry (ACT) (U01 AG 06781) Indianapolis-Ibadan Dementia Project (R01AG009956) Hardy-Myers GWAS Study Ginkgo Evaluation of Memory Study (GEMS); (5U01AT000162) Sample Types Received # Sampled Subjects Transferred DNA 3,188 Cell lines and DNA; DNA (Blood) Transferred DNA and plasma aliquots Transferred DNA and WGA DNA aliquots Transferred DNA, plasma and serum aliquots 1, ,069

21 ADNI Studies Study Alzheimer s Disease Neuroimaging Study (ADNI) (U01AG024904) Amyloid Imaging VMCI and Analysis for ADNI (ADNI-GO)(U01AG024904) And Alzheimer s Disease Neuroimaging Study (ADNI-2) (U01AG024904) Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer s disease (AD) in Veterans with mild cognitive impairment (MCI) using the Alzheimer s Disease Neuroimaging Initiative (ADNI-DoD) (W81XWH ) ADNI Depression Sample Types Received Yellow tops for cell lines and DNA Transferred DNA aliquots Yellow tops for cell lines and DNA; Purple tops and buffy coats for genomic DNA PAXgene tubes for RNA Yellow tops for cell lines and DNA; Purple tops and buffy coats for genomic DNA PAXgene tubes for RNA Yellow tops for cell lines and DNA; Purple tops and buffy coats for genomic DNA and plasma PAXgene tubes for RNA Red tops for serum Purple tops for telomere assays # Sampled Subjects 821 1,

22 FTD Studies Study Four Repeat Tauopathy Neuroimaging Initiative (4RTNI) (1R01AG ) Identification of Genetic Risk Factors for AD and FTD (GIFT) (R01AG026938) The Frontotemporal Lobar Degeneration Neuroimaging Initiative (NIFD) (R01AG32306) Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) (U54NS092089) Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) (U01AG045390) Sample Types Received # Sampled Subjects Cell lines and DNA 75 Cell lines and DNA DNA (blood) 1,471 Cell lines and DNA 151 CSF aliquots Plasma aliquots Buffy coat Buffy coat PBMCs Plasma aliquots Serum aliquots PAXgene tubes for RNA CSF aliquots Just starting 3

23 NCRAD and Dementia Research NCRAD banks samples for the ADCs NCRAD provides banking services to dementiarelated studies NCRAD can provide input during the study design/grant writing period

24 Acknowledgements NCRAD Staff Kelley Faber Ashley Vetor Kelly Horner Drew Mitchell Colleen Mitchell Chris Hobbick Alzheimer s Disease Centers Studies contributing samples to NCRAD NACC NIAGADS ADGC NIA NCRAD Executive Committee Deborah Blacker (Chair) Steve DeKosky Bernie Devlin Alison Goate David Holtzman Bud Kukull Richard Mayeux Rosa Rademakers Gerard Schellenberg Julie Schneider Replication Working Group Richard Mayeux Sudha Seshadri

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